2^nd International Conference and Expo on Lipids: Metabolism, Nutrition & Health October 03-04, 2016 Orlando, Florida, USA

Biography:

Chunfa Huang has completed his PhD from Xiamen University and postdoctoral studies at Wake Forest University School of Medicine and University of Texas Southwestern Medical Center. He was highly trained in  lipid metabolism  and cell signaling as a graduate student and as a post-doctor. Over the decades, his research area focuses on defining novel signaling pathways that regulate lipid metabolism and that are associated with human diseases including cancer., and has published more than 50 papers in reputed journals. 

Abstract:

      Cholesterol       plays an important role in cancer de velopment,      drug resistance      and chemoi mmuno-sensitivity.      Statins     , cholesterol lowering drugs, can induce apoptosis, but also negatively interfere wit h CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo      immunotherapy      of chronic lymphocytic leukemia (CLL). We used MEC-2 cells, a CLL cell line, and the peripheral blood     mononuclear     cells (PBMCs) from    CLL    patients, treated them with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol le vels, CD-20 expression and distribution, a nd cell viability in the presence or absence of fludarabine,    rituximab    or their combinations. We found that MEC-2 cells treated with cholesterol lowering  agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular   cholesterol   levels, but also significantly promoted CD-20 surface expression. Furt hermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced   chemoimmuno-sensitivity   of the PBMCs from CLL patients. Our data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20  epitope  presentation or its downstream signaling. These results provide a n   ovel strategy which could be applied to CLL treatment.

Biography:

Ian James Martins is a reviewer for various journals and was appointed as the Chief Editor for Scientific and Academic Publishing (2013/2014). Research Gate’s analysis of Dr Martins publication stats places the RG score higher than 93% of the international researchers. Dr Martins is a Fellow at Edith Cowan University/Honorary Senior Fellow (University Western Australia). Over eating and prevention by food restriction improves liver   lipid metabolism   and nature of  fat  consumed is important to improving health with contribution to biology of food restriction and maintenance of the peripheral sink abeta hypothesis and its relevance  to organ suicide, diabetes and Alzheimer’s d isease.  

Abstract:

Interventions to the aging process involve early calorie restriction with appetite regulation connected to appropriate genetic mechanisms that involve mitochondrial    biogenesis    and   DNA repair   in cells. In the aging process as the anti-aging genes are suppressed as a result of transcriptional dysregulation chronic disease accelerates and is connected to insulin res istance and   neurodegenerative  . Interests in the gene-environment interaction indicate that the anti-aging gene Sirtuin 1 (Sirt 1) that regulates food intake has been repressed early in the aging process in various global populations. The connections between Sirt 1 and other anti-aging genes such as Klotho, p66shc (longevity protein) and Forkhead box proteins (FOXO1/FO XO3a) have been connected to  lipid metabolism  and alterations in these ant i-aging genes regulate glucose, lipid and amyloid beta metabolism. Appetite regulation by nutritional intervention is required early in life that involves Sirt 1 circadian clock gene expression with Sirt 1 maintenance of other cellular anti-aging genes involved in cell metabolism and  apoptosis . Interests in anti-aging therapy with appetite regulation improves an individual’s survival to metabolic disease induced by gene-environment interactions by maintenance of the anti-aging genes connected to the metabolism of cholesterol, bacterial lipopolysaccharides, drugs and xenobiotics.  

Biography:

In December 2012, Mesut got his PhD degree from Christer S. Ejsing's lipidomics lab at University of Southern Denmark. Here he developed quantitative shotgun  lipidomics  platform for functional studies of yeast and mammalian cells lipidome. Right, after that he joined Andrej Shevchonko's lab MPI-CBG, Dresden Germany. Here he continued his work on shotgun lipidomics and additionally he deve loped a LC-MS based platform for quantification and discovery of endocannabinoids, small lipids. In 2015, he got offered to start a lipidomics lab at Danish Cancer Society Research Center (DCRC) and since 2015 he has been head of Lipidomics Core Facility (LCF) at DCRC.

Abstract:

  Lipids   are essential molecules of every living organism. Lipids assemble bilayers, determine the architectu re of  cellular  membr anes, and orchestrate numerous biological processes. Every living organism is equipped with m etabolic pathways that produce structurally and functionally highly diverse lipid species. The manners of regulations in lipid  metabolism  are poorly illuminated, yet of pivotal importance since imbalance in the lipid metabolism has been linked to pathophysiology o  f numerous diseases. The lipidome – the lipid repertoire of biological materials – includes species that differ in types of head groups, presence, length, and number of  fatty acyl  chains, numbers and positions of double bonds, and presence of additional modifications such as glycosylation and hydroxylation  etc. Obviously the combination of these gives rise to thousands of lipid species. Lipidomics methodologies enable to monitor lipid metabolism via systematic and quantitative measurements of individual lipid species in complex mixtures. Here, we present the shotgun lipidomics methodology, an advanced  mass spectrometry -based approach that enables absolute quantification. Shotgun lipidomics allows in a single setup to identify and quantify hundreds of lipid species belonging to 15-20 lipid classes. In brief, sample lipids are extracted into organic solvents and directly infused into  mass spectrometer  via electrospray ionizatio n. Lipids are separated and identified based on the unique mass to charge  ratios of their ions and fragmentation patterns, and absolutely and accurately quantified against internal standards. The simple and robust setup makes this approach particularly suited for high throughput lipidomics analysis. The typical workflow, challenges, and considerations on the shotgun lipidomics will be highlighted.

Biography:

Marica Bakovic completed BSc in Chemistry and PhD in     Biological Chemistry     at the University of Alberta. She received post-doctoral awards from Medical Research Council and Alberta Heritage Foundation. Before com ing to the University of Guelph, she worked in the area of molecular and    cell biology    of   lipid   metabolism at the Faculty of Medicine, University of Alberta. C  urrently, she is Professor in the Department of   Human Health   and  Nutritional Sciences  at the University of Guelph. Dr. Bakovic has a long-lasting  interest in lipid metabolism and nutrition, especially in the area of regulation of membrane phospholipids,  fatty acids , and methyl-group donors.  

Abstract:

Phospholipids play an indispensable role in heart function via their structural and metabolic roles, and serve as a barrier that protects the intracellular cell environment.  The first evidence of mammalian heart dysfunction in relation to deregulated phospholipid synthesis by the CDP-ethanolamine Kennedy pathway came from our recent study with CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) heterozygous mice ETKO. ETKO mice of both genders have reduced phosphatydylethnolamine (PE) synthesis and turnover, accumulate plasma and tissue triglycerides and develop insulin resistance. However, only ETKO males develop age-related cardiac hypertrophy and hypertension. The underlying mechanism for the male specific dysfunction was identified in the accumulation of arachidonic acid and other n-6 elongation/desaturation pathway intermediates in the male heart membranes and reduced circulating testosterone levels. There is a clear sexual dimorphism in the heart phospholipids and the sex-related differences expand to the heart neutral lipids but not cardiolipin. Dysfunctional Pcyt2 gene (reduced PE synthesis and turnover) causes insulin resistance in both males and females, however specifically perturbs membrane metabolism protecting the female heart and causing the male-specific diabetic cardiomyopathy. We explore the nature of those differences to show what role Pcyt2 plays in cardiac cell function, signaling, and gene expression and how they contribute the male-specific hypertension and heart pathology.

Biography:

Sampath Parthasarathy MBA, PhD , was instrumental in the development of the concept of oxidized   LDL   and its contribution to  atherosclerosis , a major form of cardiovascular disease. He is currently at University of Centr al Florida as the F lorida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Research. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for lipids and the Ranbaxy Award for excellence in cardiovascular research.
 

Abstract:

Apolipoprotein (Apo A1) and apolipoprotein E (Apo E) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. Based on the nature of the peptide, we predicted that these effects could be attributed to their positively charged amino acid residues and hydrophobicity. Accordingly, we designed and tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins, neutralize the charge of negatively charged modified lipoproteins, and inhibit the latter’s uptake by macrophages. As bacterial lipopolysaccharide (LPS) is also a highly negatively charged molecule, we also tested the peptides to affect LPS induced macrophage inflammatory response. 

5F-mimetic peptide of apoA1, LL27 derived from the anti-microbial peptide CAMP, and a human glycodelin derived peptide was commercially synthesized. The number of positively charged amino acid residues (K+R) and negatively charged residues (D+E) were 4/4, 7/4, 6/2 respectively. Their abilities to reduce lipid peroxides (LOOH), inhibit the oxidation lipoproteins (LDL & HDL), interact with modified lipoproteins, and to inhibit macrophage uptake of modified LDL and inflammation were analyzed.  Their abilities to inhibit LPS and Ox-LDL induced inflammatory responses also were determined.

Cationic peptides decomposed 13-HPODE and inhibited the oxidation of LDL in a lysine dependent manner. Incubation of Ox-LDL and Ac-LDL with the peptides resulted in charge neutralization. Pre-incubation of the peptides with modified lipoproteins reduced the uptake of the latter by macrophages and foam cell formation as detected by Oil-Red O staining. Increased inflammatory gene expressions were observed in the presence of LPS/Ox-LDL. However, peptides inhibited the Ox-LDL-induced inflammatory gene expressions but showed a dual effect on LPS induced inflammatory response. In contrast, native LDL, which has several positively charged domain formed complexes with Ox-LDL and increased macrophage cholesterol accumulation.

Based on these studies, we suggest that cationic peptides may be a valuable tool for controlling Ox-LDL mediated inflammation and atherosclerotic progression. However, the Ox-LDL, in the presence of native LDL might be more atherogenic and suggest a potential competition between soluble peptides and intact lipoproteins.

Biography:

Sandile Fuku completed his Doctoral studies in   Biomedical   Technology from the Central University of Technology and  is currently a Postdoctoral fellow in the Department of  Biochemistry,  at North-West University. Currently, his research is on  epigenetic regulation in metabolic syndromes, particularly focusing on  diabetics  and cancer. He has published work in cancer treatment, diabates and phytochemistry  .

Abstract:

Background

Activation of Calmodulin dependent protein kinase (CaMK)II by exercise has plethora of benefits in metabolism and health.  Regulation of lipid metabolism is very significant to alleviate type 2  diabetes and obesity.  The role of CaMKII in the regulation of genes that are involved in lipid metabolism has not been studied yet, which became the focus of this study.

Methods

Five to six weeks old male Wistar rats were used in this study.  Western blot was performed to assess the protein expression of Carnitine palmitoyltransferase (CPT)-1 and Acetyl-CoA carboxylase (ACC)-1.  Cpt-1 and Acc-1 gene expressions were assessed using Quantitative real time PCR (qPCR).    

Results

The results indicate that exercise-induced   CaMKII   activation increases CPT-1  expression   and decreases ACC-1 expression in rat skeletal m  uscle.  Thus, confirming CaMKII activation by exercise and the resultant increase in  lipid  oxidation.     Administration of KN93 (CaMKII inhibitor) reversed all exercise-induced changes.  

Conclusions

This study demonstrated that CaMKII activation, by exercise, regulates lipid    metabolism      genes   in rat ske letal  muscle .  Fur ther, the increase in lipid oxidation and decrease in   lipi d   synthesis are evidence of the regulatory role CaMKII in lipid metabolism. CaMKII is a potential target in designing novel   therapeutic   drugs in the management and treatment of  type 2 diabetes  and obesity.  

Biography:

Abstract:

The burden of    cardiovascular disease    (CVD) in Indian population is high regardless of their country of residence. World Health O rganisation estimates 60% o world’s   cardiac   patients will be Indians with 50% 0 f   CVD   related deaths occurring in patients below 70y compared to 23% in the West. Indian ethnicity is regarded as a non modifiable risk factor by CVD prevention guidelines. 

The mission of the LAI expert consensus statement on management of   dyslipidaemia   is to address early onset and higher risk for CVD in this population by simplifying the process of identification at an early age as well as to  intensify treatment to aggressively mange risk factors including life style changes at a lower risk levels compared  to other global guidelines.

The choice of a lower target of   LDL   C of <50 mg/dl and non-HDL C o <80 mg/dl for the high risk group as well as secondary prevention will help India achieve the expected reduction in CVD. Adoption of Non HDL-C a s a co primary target will address  atherogenic  lipoprotein pattern that incorpora  tes the low HDL and high Triglyceride level in this population. The consensus statement recommends a lower threshold for not using statin at <5% but the use of life time risk assessment in this group. Reducing the age threshold for screening for CVD risk to 18y (at ent ry to university education) is likely to have a greater impact in reducing the CVD epidemic.

While considerable success is seen with the effort taken by LAI to implement the advice to Indian physicians, adoption of this expert advice by governmental bodies, other professional organisation within and outside India will provide a greater impetus to reduce premature CVD in this high risk population irrespective of their place of residence.

Biography:

Laura Bindila is Head of  Lipidomics /Mass Spectrometry Facility at the Institute for Physiological Chemistry, University Medical Center Mainz, where her scie ntific interest is unravelling the lipid signals involved in various neurobiologica l processes, and more generally in physiological and pathophysiological states. She is also a member of Research Center for Translational Neuroscience, of the University of Mainz. She has previously worked at Luxembourg Clinical Proteomics, and University of Münster where she has focused on glycoconjugates an d (glyco)proteomics in cancer research and rare diseases.

Abstract:

      Lipids       are molecular components which play essential roles in many physiological processe s and      pathological      condi tions, including      neurodegenerative      , metabolic, immune diseases. The     lipids     serve not only a constitutive rol e in the cell membrane, but also as the  source for downstream signaling molecules, such as      endocannabinoids      or eicosannoids that underscore essential     neurobiological     functions. In neurobiology research lipids emerge as important cand idates for     biomarkers    , drug targets, but also as therapeutic agents. To gain a better understanding of their specific functio ns and to define the    signaling    networks, especially  under    pathological    conditions, accurate identification and quantification of lipids, as well as profiling of other molecular correlat es such as related   genes   and  proteins  in on  e and the same tis  sue source is essential. In addition, (sub)localization of disease-associated lipid changes within and across tissue regions is essential to expedite the unravellign of disease mechanisms, as well as discovery of lipid-based  drug  targets and lipid-based therapeutic agents.   

Here, advanced  lipidomic  strategies, combining quantitative mass spectrometry with high-throughput sample preparation for multiplex lipid analysis in minute amount of biological matrices, that enable translation of pr e(clinical) features of neurological disorders into quantita tive neurolipidomics will be discussed. 

Biography:

Dr. Siddiqi is an Associate Professor at the UCF College of  Medicine  and earned his Ph.D. at Central Drug Research Institute/Lucknow University i n India. He did post-doctoral training at the National Institute of Immunology in India and the Gastroenterology Division, University of Tennessee  Health Science Center. His research is focused on deciphering the cellular and molecular mechanisms underlying the lipid metabolism. His major contribution to the field is the discovery of a new paradigm for the ER-to-Golgi transport of nascent lipoproteins. He serves on editorial boards of several journals and as a reviewer for numerous journals.  
 

Abstract:

Secretion of   lipids   in the form of very low-density lipoproteins (VLDL) by the liver plays an important role in maintaining  overall body lipid  homeostasis . Any abnormality a ssociated with this physiological process can lead to severe metabolic disorders such as  hyperlipidemia , hepatic steatosis etc. The rate-limiting step in the secretion of VLDLs from the liver is their transport from the endoplasmic reticulum (ER) to the Golgi and represents a  potential therapeutic target in controlling VLDL secretion. We have identified a distinct ER-derived vesicle, VLDL transport vesicle (VTV), which facilitates the targeted delivery of VLDLs from the ER to the Golgi. To find out the factors that regulate the biogenesis of these vesicles, we performed detailed proteomic and  biochemical  analyses. Our data revealed that two small Mr proteins, cideB and SVIP are present in VTV but not in other ER-derived vesicles. Our morphological and co-immunoprecipitation data revealed that both cideB and SVIP specifically interact with VLDL  structural protein , apolipoproteinB100. To examine the roles of these proteins in VTV-biogenesis, we carried out an in vitro ER-budding assay. We show that either blocking or knockdown of cideB and SVIP abrogates VTV-budding and VLDL secretion from  hepatocytes . We conclude that cideB and SVIP control VLDL/lipid secretion from the liver by regulating VTV-formation and their identification is critical for the development of novel therapeutics for dyslipide mia.

Biography:

Michal Masternak has completed his PhD at the age of 26 years from Poznan University of  Medical Sciences  and postdoctoral studies from Southern Illinois University, School of Medicine in Springfield , IL. He is an Associate Professor at Univerist of Central Florida. He has published more  than 76 papers in reputed journals and has been serving as an editorial board member in several scientific journals.

Abstract:

Studies of mice with growth hormone (GH) deficiency or resistance have shown that disruption of the GH axis promotes     insulin     sensitivity, improves    glucose metabolism    and is strongly associated with extended longevity and delayed aging. Long-living GH receptor knockout (GHRKO) and GH-defic ient Ames dwarf (df/df) mice are    obese    and more importantly have more visceral fat than their normal counterparts, yet these mice are still very insulin sensitive. Interes tingly, our data showed that surgical   visceral fat   removal (VFR) decreased  insulin  sensi  tivity and glucose tolerance in long-living, obese GHRKO and df/df mice in comparison to sham controls, while the same intervention improved insulin sensitivity and glucose tolerance in N mice. Additionally, VFR intervention improved insulin signaling p athway in skeletal muscle in normal mice only, without any alterations in GHRKO animals. We also found that the transplant of visceral fat from GHRKO mice to N mice (N-GHRKO) improved whole body insulin sensitivity when comparing with  sham-operated  mice (N-S) and with mice that received visceral fat from N mice (N-N). Observed improvement of insulin sensitivity was associated to increased phosphorylation levels of insulin receptor and increased expression of  Pparα and Pparγ in the liver.These findings show that the same endocrine organ plays different role on insulin sensitivity in GHRKO and df/df mice when comparing with N control mice. We hypothesize that this divergent role of VF is due to different secretory pattern in visceral fat, which is mediated by suppression of GH action in adipose tissue.

Biography:

Sampath Parthasarathy MBA, PhD , was instrumental in the development of the concept of oxidized LDL and its contribution to   atherosclerosis  , a major form of  cardiovascular disease . He is currently at University of Central Florida as the Florida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Resea rch. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for  lipids  and the Ranbaxy Award for excellence in cardiovascular research. 

Abstract:

Generation of foam cells, an essential step for reverse   cholesterol   transport (RCT) studies, uses the technique of  receptor dependent macrophage loading with radiolabeled acetylated  Low Density Lipoprotein  (Ac-LDL). In this study, we used the ability of a biologically rel evant detergent molecule,  Lysophosphatidylcholine  (Lyso PtdCho), to form mixed micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam cells. Fluorescent or radiolabelled cholesterol / Lyso PtdCho mixed micelles were prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Macrophag es incubated with  cholesterol  or CE (unlabeled, fluorescently labeled or radiolabeled) / Lyso PtdCho mixed micelles accumulated CE  as documented by microscopy, lipid staining, labeled oleate incorporatio n, and by thin layer chromatography (TLC). Such foam cells unloaded cholesterol when incubated with high density lipoprotein (HDL) and not with oxidized HDL (Ox-HDL). We propose that stable cholesterol or CE / Lyso PtdCho micelles would offer advantages over existing methods.

Using this technique we demonstrated that such macrophages mimicked biological properties attributed to  cholesterol  loaded macrophages. Earlier, we had used similar technique to enrich cells with beta carotene. We suggest that this novel technique of delivering macromolecules to the cells could be further manipulated to de liver other hydrophobic large molecular cargos to the cells.